Suppository of retaining in lower region of rectum

ABSTRACT

A suppository of retaining in a lower region of rectum, which contains a suppository base containing:
     (A) a fatty acid triglyceride,   (B) one or more C 14-18  fatty acid glycerides, and   (C) a base ingredient for retaining the suppository in the lower region of rectum, has quite high safety, does not melt by the body temperature when it is held by the fingers before insertion into the rectum so that it is easy to handle, does not deform by elevation of temperature during storage, and prevents stimulation to the rectum mucosa such as congestive hemorrhage and expansion of the rectum mucosa after the insertion.

TECHNICAL FIELD

The present invention relates to a suppository, and particularly to asuppository of retaining in the lower region of rectum. Moreparticularly, it relates to a suppository of retaining in the lowerregion of rectum free from the melting at the time of being held by thefingers and from the deformation of the suppository due to elevation oftemperature during storage.

BACKGROUND ART

It is known that a composition for administering to the rectum, which isrepresented by a usual suppository being administered to the annalregion of the rectum, moves from the site where it is administered tothe upper region of the rectum with the passage of time, because thesuppository base melted by the body temperature and liquefied. Also, aninside temperature of the rectum of human beings varies depending uponthe individual differences in body temperature. Furthermore, when thebody is affected by pyrexia or pathopoiesis of the rectum, the insidetemperature of the rectum changes within a wider range than that in anormal physiological condition of the body. Melting and spreading of asuppository at the annal region of the rectum immediately after theadministration reduce the amount of the effective ingredients existingaround the annal region of the rectum. For this reason, there have beenreported a number of suppository compositions for curing hemorrhoidswhich control the spreading of molten suppository existing around theannal region of the rectum so that the effective ingredients of thesuppository act effectively to the affected regions.

Further, in the usual suppositories, the shape of composition changeswith time due to elevation of temperature during storage, etc., and thedeformation sometimes is so serious as to make the suppository unusable.

The present applicant reported in WO99/17737 a suppository compositioncontaining a C₁₀₋₁₂ fatty acid glyceride, which can be kept unmolten inspite of the body temperature even when it is held by the fingers beforethe insertion into the rectum, melts after the insertion into therectum, but is free from further spreading of the melted suppository tothe upper region of the rectum. However, it has been found that thissuppository composition gives stimulation such as congestive hemorrhageor expansion of the rectum mucosa when incorporated with lidocaine,lidocaine hydrochloride, dibucaine, dibucaine hydrochloride, procaine,procaine hydrochloride or ethyl aminobenzoate.

DISCLOSURE OF THE INVENTION

It is an object of the present invention to provide high-safetysuppository of retaining in the lower region of the rectum, which iseasy to handle, kept unmolten in spite of the body temperature when heldby the fingers before the insertion into the rectum, free fromdeformation of the suppository caused by elevation of temperature duringstorage, free from the stimulation to the rectum mucosa, and iseffective for preventing congestive hemorrhage as well as expansion ofthe mucosa.

The present inventors have conducted various studies on suppositories ofretaining in the lower region of rectum. As a result, they have foundthat a suppository composition comprising a suppository base comprising:

-   (A) a fatty acid triglyceride,-   (B) one or more C₁₄₋₁₈ fatty acid glucerides, and-   (C) a base ingredient for retaining the suppository in a lower    region of rectum, has a melting point exceeding 50° C., can be kept    unmolten when held by the fingers before insertion into the rectum    so that it is easy to handle, and is free from the deformation of    the suppository composition caused by elevation of temperature    during storage, able to release the drug satisfactorily, prevented    from the simulation to the rectum mucosa, and is very high in    safety. Based on this finding, the present invention has been    accomplished.

When a conventional suppository composition containing a C₁₀₋₁₂ fattyacid glyceride which is kept unmolten by the body temperature of fingerswhile held on the fingers and melts just after the insertion into rectumis compounded with lidocaine or lidocaine hydrochloride, the resultingcomposition gives stimulations to the rectum mucosa to cause congestivehemorrage or expansion of the rectum mucosa. In contrast, thesuppository composition of retaining in the lower region of rectumaccording to the present invention gives no stimulation to the rectummucosa even when compounded with lidocaine, lidocaine hydrochloride,dibucaine, dibucaine hydrochloride, procaine, procaine hydrochloride orethyl aminobenzoate.

Further, the suppository of the present invention is essentially freefrom C₁₀₋₁₂ fatty acid glycerides. When a C₁₀₋₁₂ fatty acid glyceride ispresent as a subsidiary ingredient in the fatty acid triglyceride or theC₁₄₋₁₈ fatty acid glyceride, the content of the C₁₀₋₁₂ fatty acidglyceride should preferably be controlled so that it does not exceed 5%by weight based on the total weight of the suppository base, and furtherpreferably so that it is less than 1% by weight.

Furthermore, incorporation of powders insoluble in the fatty acidtriglyceride into the suppository of retaining in the lower region ofrectum improves the state of dispersing of the suppository base, whichcan eliminate the scattering in quality at the time of filling thesuppository into a container or mold, thereby to prepare the desiredsuppository.

The fatty acid triglyceride includes, for example, cacao butter, lanolinbutter, medium chain fatty acid triglycerides and hard fats. The hardfats include, for example, “Witepsol” (manufactured by Huls AmericaInc.), “Sapposier” (manufactured by Gattefosse Inc.), “Isocacao”(manufactured by Kao Corp.) and “Pharmasol” (manufactured by NOF Corp.).

The C₁₄₋₁₈ fatty acid glyceride includes myristic acid monoglyceride(glycerine ester of C₁₄ fatty acid), palmitic acid monoglyceride(glycerine ester of C₁₆ fatty acid), and stearic acid monoglyceride(glycerine ester of C₁₈ fatty acid), of which preferred are palmiticacid monoglyceride and stearic acid monoglyceride.

The base ingredient for retaining the suppository composition in thelower region of rectum is a base ingredient for administration to rectumwhich allows a drug to retain in the lower region in the vicinity ofannus of rectum. It includes, for example, acrylic acid polymers, alkalimetal salts of polygum, laminar silicic acid salt minerals, starchgrafted acylates, polyvinyl alcohols, pectins, celluloses, such asmethylcellulose and carboxymethylcellulose, etc., polyvinylpyrrolidone,“Pullulan” and tragacanth gum. Of these, one or more of acrylic acidpolymers, alkali metal salts of polygum, laminar silicic acid saltminerals and starch grafted acrylic acid are preferable; and acrylicacid polymers are particularly preferable. Of acrylic acid polymers,carboxyvinyl polymers are most preferable.

The powders insoluble in the fatty acid triglyceride include, forexample, anhydrous silicic acid, starches, crystalline celluloses, zincoxide and alginic acid. Of these, anhydrous silicic acid is preferable.

When the total weight of suppository base is taken as 100% by weight,

-   (A) the amount of the fatty acid trigluceride ranges preferably    50–90% by weight and further preferably 65–85% by weight based on    the total weight of the suppository,-   (B) the amount of the oily base consisting of one or more kinds of    C₁₄₋₁₈ fatty acid ester of glycerine is preferably 5–30% by weight    and further preferably 6.5–13% by weight based on the total weight    of the suppository, and-   (C) the amount of the base ingredient for retaining the composition    in a lower region of rectum ranges preferably 0.1–20% by weight    based on the total weight of the suppository. As ingredient (C),    acrylic acid polymers are preferable and carboxyvinyl polymer is    more preferable. The amount thereof ranges preferably 0.2–15% by    weight and further preferably 1–10% by weight based on the total    weight of the suppository.

The amount of lidocaine, lidocaine hydrochloride, dibucaine, dibucainehydrochloride, procaine, procaine hydrochloride or ethyl aminobenzoateranges preferably 0.1–20% by weight when the total weight of thesuppository is taken as 100% by weight.

The amount of the powder insoluble in the fatty acid triglyceride rangespreferably 0.1–20% by weight and further preferably 0.5–10% by weight,when the total weight of the suppository is taken as 100% by weight.

Various drugs can be formulated with the suppository of retaining in thelower region of rectum according to the present invention. The drugsreferred to here are those which can generally be administered to therectum. They include, for example, angiotenic agents, such as“Tetrahydrozoline” hydrochloride, “Naphazoline” hydrochloride,“Phenylephrine” hydrochloride, ephedrine hydrochloride and“Oxymetazoline” hydrochloride; anti-inflammatory, antipyretic, oranalgesic agents, such as acetylsalycilic acid, acetoaminophenone,“Buprenorphine” hydrochloride, “Ibprofen”, “Ketoprofen”, “Proxicam”,morphine hydrochloride, lysozyme chloride and glycylrrhetinic acid;antibiotics such as penicillin antibiotics, cephalosporin antibiotics,“Tetracycline” antibiotics and macrolide antibiotics; antineoplasticagents, such as 5-fluorouracil and “Ftorafur”; antifungal agents, suchas “Econazole”, “Econazole” nitrate, “Miconazole”, “Miconazole” nitrate,“Clotrimazole”, “Bifonazole”, “Terbinafine” hydrochloride and“Butenafine” hydrochloride; steroid preparations, such ashydrocortisone, hydrocortisone acetate, predonisolone, predonisoloneacetate, “Dexamethasone” and “Dexamethasone” acetate; local anestheticssuch as tetracaine, mepivacain, chloprocaine, bupivacain, proparacain,phenacaine, cocaine, oxyprocain, propitocaine, orthocaine, oxethazaine,tetracaine hydrochloride, mepivacain hydrochloride, chloroprocainehydrochloride, bupivacain hydrochloride, proparacain hydrochloride,phenacaine hydrochloride, cocaine hydrochloride, oxyprocainhydrochloride, propitocaine hydrochloride, “Meprylcaine” hydrochlorideand “Mepivacaine”; astringents such as zinc oxide, tannic acid, albumintannate and aluminum potassium sulfate; antihistamic agents such asdiphenhydramine, diphenhydramine hydrochloride and chlorphenylaminemaleate; accelerating agents for curing wound, such as allantoin,aluminum chlorohydroxy allantoinate; antiseptics, such as“Chlorhexidine” hydrochloride, “Cetrimide”, “Dequalinium” chloride andbenzalkonium chloride; sulfa drugs, such as “Sulfisomidine”,“Sulfisomidine sodium”, “Homosulfamine”, and “Sulfadiazine”; vitamins,such as cod liver oils, ergocalciferol, riboflavin, pyridoxinehydrochloride and tocopherol acetate; refrigerants such as d-camphor,dl-camphor, l-menthol, dl-menthol, mentha oil and eucalyptus oil;antiemetics such as “Donperidone”; accelerating agents of defectation,such as “Bisacodyl”; bronchodialators such as theophylline; and peptidessuch as insulin, etc.

The suppository of the present invention can be prepared by melt-mixinga fatty acid triglyceride, an oil base consisting of a combination ofone or more C₁₄₋₁₈ fatty acid glycerides and an ingredient for retainingthe suppository deposited in the lower region of rectum, and ifnecessary, powders insoluble in the fatty acid triglycerides, addingthereto drugs and additives, uniformly mixing and stirring the resultingmixture, and filling the mixture in a container, mold or the like, andcooling and solidifying the filling. The method for mixing is notspecifically restricted.

INDUSTRIAL APPLICABILITY

The present invention relates to a suppository composition particularlyuseful for treatment of hemorrhoids. More particularly, the presentinvention relates to a suppository composition of retaining in a lowerregion of the rectum into which is compounded a suppository basecomprising:

-   (A) a fatty acid trigluceride,-   (B) one or more kinds of C₁₄₋₁₈ fatty acid glucerides, and-   (C) a base ingredient for retaining the composition in a lower    region of rectum. The composition of the present invention is used    as a high-safety suppository for retaining in the lower regions of    rectum, which is kept unmolten by the body temperature of fingers    when held by the finger before the insertion to rectum, stable to    the elevation of temperature during storage, and free from    stimulation to the rectum mucosa even when compounded with    lidocaine, lidocaine hydrochloride, dibucaine, dibucaine    hydrochloride, procaine, procaine hydrochloride and ethyl    aminobenzoate.

EXAMPLES

The present invention will be explained in more detail with reference tothe following examples and test examples.

Example 1

(Recipe) Tetrahydrozoline hydrochloride   1.0 g Lidocaine  60.0 gHydrocortisone acetate   5.0 g Allantoin  20.0 g Tocopherol acetate 60.0 g Light anhydrous silicic acid  20.0 g Carboxyvinyl polymer  34.0g Myristic acid monoglyceride  217.5 g Witepsol H15 1232.5 g(Preparation Method)

A suppository base (myristic acid moonoglyceride and Witepsol H15) washeated and molten (at 50 to 70° C.). Then other ingredients weresuccessively added to the melted suppository base and dispersed thereinwhile stirring. The resulting mixture was cooled, filled in asuppository container, and further cooled and molded to obtain anintended suppository.

Example 2

(Recipe) Phenylephrine hydrochloride   4.0 g Lidocaine  82.5 g Lightanhydrous silicic acid  20.0 g Carboxyvinyl polymer  34.0 g Myristicacid monoglyceride  226.4 g Pharmasol B115 1283.1 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Example 3

(Recipe) Phenylephrine hydrochloride   1.0 g Menthol  10.0 gCarboxyvinyl polymer  20.0 g Myristic acid monoglyceride  126.0 gPalmitic acid monoglyceride  32.0 g Witepsol H15 1424.0 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Example 4

(Recipe) Naphazoline hydrochloride   1.0 g Lidocaine  60.0 gPrednisolone acetate   1.0 g Allantoin  20.0 g Tocopherol acetate  60.0g Carboxyvinyl polymer  34.0 g Laponite  70.0 g Stearic acidmonoglyceride  74.0 g Witepsol H15 1400.0 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Example 5

(Recipe) Phenylephrine hydrochloride   4.0 g Lidocaine  82.5 g Zincoxide   8.5 g Light anhydrous silicic acid  20.0 g Carboxyvinyl polymer 34.0 g Myristic acid monoglyceride  214.0 g Pharmasol B115 1213.0 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Example 6

(Recipe) Hydrocortisone acetate   5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  33.0 g Light anhydrous silicic acid  20.0 g Myristic acidmonoglyceride  229.8 g Witepsol E85  260.4 g Witepsol W35 1041.8 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Example 7

(Recipe) Hydrocortisone acetate   5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  33.0 g Light anhydrous silicic acid  20.0 g Myristic acidmonoglyceride  229.8 g Witepsol E85  260.4 g Witepsol W35 1041.8 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Example 8

(Recipe) Hydrocortisone acetate   5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  33.0 g Light anhydrous silicic acid  20.0 g Palmitic acidmonoglyceride  76.6 g Stearic acid monoglyceride  153.2 g Witepsol E85 260.4 g Witepsol W35 1041.8 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Example 9

(Recipe) Hydrocortisone acetate   5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  33.0 g Light anhydrous silicic acid  20.0 g Palmitic acidmonoglyceride  153.2 g Stearic acid monoglyceride  76.6 g Witepsol E85 260.4 g Witepsol W35 1041.8 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Example 10

(Recipe) Hydrocortisone acetate   5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  33.0 g Light anhydrous silicic acid  20.0 g Palmitic acidmonoglyceride  149.9 g Witepsol E85  269.8 g Witepsol W35 1079.3 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Example 11

(Recipe) Hydrocortisone acetate   5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  66.0 g Light anhydrous silicic acid  20.0 g Stearic acidmonoglyceride  149.9 g Witepsol E85  269.8 g Witepsol W35 1079.3 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Example 12

(Recipe) Hydrocortisone acetate   5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  66.0 g Light anhydrous silicic acid  20.0 g Palmitic acidmonoglyceride  75.0 g Stearic acid monoglyceride  75.0 g Witepsol E85 269.8 g Witepsol W35 1079.3 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Example 13

(Recipe) Hydrocortisone acetate   5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  66.0 g Light anhydrous silicic acid  20.0 g Palmitic acidmonoglyceride  60.0 g Stearic acid monoglyceride  60.0 g Witepsol E85 275.4 g Witepsol W35 1103.7 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Comparative Example 1

(Recipe) Hydrocortisone acetate  5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  33.0 g Light anhydrous silicic acid  20.0 g Capric acidmonoglyceride 163.8 g Lauric acid monoglyceride 491.4 g Witepsol H15982.9 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Comparative Example 2

(Recipe) Hydrocortisone acetate   5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  33.0 g Light anhydrous silicic acid  20.0 g Lauric acidmonoglyceride  245.7 g Witepsol H15 1392.4 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Comparative Example 3

(Recipe) Hydrocortisone acetate   5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  33.0 g Light anhydrous silicic acid  20.0 g Lauric acidmonoglyceride  306.4 g Witepsol H15 1225.6 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Comparative Example 4

(Recipe) Hydrocortisone acetate   5.0 g Lidocaine  60.0 g Carboxyvinylpolymer  65.0 g Light anhydrous silicic acid  20.0 g Witepsol E85  300.0g Witepsol H15 1200.0 g(Preparation Method)

The suppository was prepared by the similar method as in Example 1.

Test Example 1 Test on Stimulation to Rectum Mucosa Test Method

As the test samples, the suppository compositions of rectum-retainingtype according to Examples 6–13 of the present invention and thesuppository compositions of Comparative Examples 1–3 in which a C₁₀and/or C₁₂ fatty acid glyceride was compounded were used. In all thetest samples, each suppository weighed about 1.65 g. In the test group,Japanese white strain male rabbits (body weight: 3.0–3.5 Kg) were used.The rabbits were in good systemic condition without having diarrheaafter fasted for 48 hours. Two or three rabbits were used for each ofthe suppository test samples.

Method of administration of the suppository test sample was as follows.Thus, one grain of a suppository test sample was inserted into therectum of the rabbit fasted for 48 hours beforehand, then the anus ofthe rabbit was pressed by the finger of an experimenter for several tenseconds for the purpose of preventing escape of the insertedsuppository, further the anus was closed and sealed tightly by use of anadhesive (Alon-alpha GEL-10: manufactured by Toagosei Co. Ltd.). Therabbit was allowed to water freely until autopsy.

(Observation of the Stimulation to the Rectum Mucosa:)

5 Hours after the administration of suppository test sample, the rabbitsin each of the test groups were subjected to euthanasia by bleeding fromthe carotid artery under anesthesia with pentobarbital. The intestinesinvolving rectum and colon were enucleated from the anus. The enucleatedintestines were incised. The mucosal membranes of intestins were washedwith physiological saline. Thereafter, the incised intestines wereextended on a flat plate, and the mucosal membranes were macroscopicallyobserved. Congestive hemorrhage and expansions appearing on the rectummucosa were examined by macroscopical observation, and the results wererated as stimulation scores. The stimulation scores were defined asfollows:

Score No change: 0 Little change: 1 Slight change: 2 Mediocre change: 3Marked change: 4(Test Results:)

Test results are shown in Table 1.

TABLE 1 Stimulation scores Example 6 Example 7 Example 8 Example 9 Score2 2 2 2 2 0 0 0 1 Example 10 Example 11 Example 12 Example 13 Score 0 00 0 0 0 0 0 0 Comparative Comparative Comparative Example 1 Example 2Example 3 Score 2 3 3 4 4 3 4 2 1

The suppositories of Comparative Examples 1–3 gave a mediocre or markedstimulation such as congestive hemorrhage and expansions to the rectummucosa. The suppositories of Examples 6–13 according to the presentinvention, however, gave no stimulation or gave only a slightstimulation to the rectum mucosa. Thus it has been proved that thesuppositories of the present invention are much higher in safety thanthe suppositories of comparative examples.

Test Example 2 Measurement of Melting Point of Suppository

Test Method:

As the test samples, the suppositories of Examples of 8–13 according tothe present invention and the suppository of Comparative Example 4 as aconventional suppository of retaining in the lower region of rectum wereused. The melting points were measured by means of Automatic DroppingMelting Point Measuring Apparatus (FP80 and FP83, manufactured byMettler Corp.). Each sample was filled into a cup having a diameter of6.35 mm and the temperature was elevated at a rate of 0.2° C./minute.The dropping softening point (° C.) was taken as the melting point.Results:

The melting points determined are listed in Table 2.

TABLE 2 Melting point (° C.) Example 8 Example 9 Example 10 Meltingpoint 58.3 57.0 55.0 Comparative Example 11 Example 12 Example 4 Meltingpoint 56.0 54.7 38.7

Melting points of the suppositories of Examples 8–12 according to thepresent invention exceeded 50° C. Melting point of the suppository ofComparative Example 4 was lower than 40° C.

The results shown above demonstrate that the suppositories of Examples8–12 according to the present invention have a melting point much higherthan the body temperature of human beings, and therefore thesesuppositories are entirely free from the risk of melting while beingheld on figures before insertion into the rectum. In contrast, thesuppository of Comparative Example 4 has a risk of melting while it isheld between fingers when the body temperature is high due to pyrexia.Further, the suppository of Comparative Example 4 has a risk ofdeforming its shape due to softening or melting if temperature risesunder the condition of storage, while the suppositories of Examples 8–12according to the present invention are free from deformation due tosoftening so far as the elevation in temperature does not exceed thatunder usual conditions of storage. Accordingly, it has been proved thatthe suppositories of the present invention are excellent in the handlingproperty.

Test Example 3 Measurement of Drug-Releasing Rate

Test Method:

A drug-releasing test was carried out by the use of Elution Tester(manufactured by Toyama Sangyo Co., Ltd.) used according to the secondmethod of Method for Elutioh Test, Japanese Pharmacopoeia (paddlemethod). As the test solution, 900 ml of phosphate buffer solution (pH7.2) was used. The speed of rotation of the paddle was 100 rpm. Asuppository was packed within an area having a width of 5 cm in amembrane filter (Dialysis Membrane, Size 36; manufactured by Wako PureChemical Industries, Ltd.) previously immersed in the buffer solution bythe use of two closers. The test was carried out at 37° C., and 1 mlportion was sampled out every one hour. The test was continued till theoverall time of test reached 6 hours. The samples taken werequantitatively analyzed by HPLC.

Conditions of HPLC Quantitative Analysis Column: ODS-80 Ts (Tosoh Corp.)Column temperature: 50° C. Mobile phase: Methanol:Water:PhosphoricAcid:Sodium Laurate = 60:40:0.1:0.5 Flow rate: 1 ml/min. Injectionamount: 1 μl Wavelength of detection: 220 nm

As the samples, the suppositories of Examples 13–16 of the presentinvention and the suppository of Comparative Exampel 4 were used.

Lidocaine

Results:

TABLE 3 Drug releasing rate (%) Example 13 Example 14 Example 15 Release(%) 45.1 39.0 32.1 Comparative Example 16 Example 4 Release (%) 40.338.8

The suppositories of Examples 13–16 according to the present inventionshowed a good lidocaine-releasability comparable to that of thesuppository of Comparative Example 4. Accordingly, it has been provedthat the suppositories of the present invention have no problem withregard to drug-releasability.

1. A suppository comprising a suppository base and one or more activeingredients selected from the group consisting of lidocaine, lidocainehydrochloride, dibucaine, dibucaine hydrochloride, procaine, procainehydrochloride and ethyl aminobenzoate; wherein said suppository basecomprises: (A) a fatty acid triglyceride in an amount of from 50–90% ofthe total weight of the suppository base, (B) one or more C₁₄₋₁₈ fattyacid glycerides in an amount of from 5–30% of the total weight of thesuppository base, wherein said one or more C₁₄₋₁₈ fatty acid glyceridesis selected from the group consisting of myristic acid monoglyceride,palmitic acid monoglyceride and stearic acid monoglyceride, and (C) abase ingredient for retaining the suppository in a lower region of arectum, wherein said base ingredient is present in an amount of from0.1–20% of the total weight of the suppository base, and said baseingredient is one or more members selected from the group consisting ofan acrylic acid polymer, an alkali metal salt of polygum, a laminarsilicic acid salt mineral, a starch grafted acylate, a polyvinylalcohol, a pectin, a cellulose, a polyvinylpyrrolidone, a pullulan, anda tragacanth gum; wherein total C₁₀₋₁₂ fatty acid glyceride in thesuppository base does not exceed 5% of the total weight of thesuppository base.
 2. A suppository according to claim 1, wherein saidbase ingredient for retaining the suppository in the lower region of therectum is one or more members selected from the group consisting of anacrylic acid polymer, an alkali metal salt of polygum, a laminar silicicacid salt mineral, and a starch-grafted acrylic acid.
 3. A suppositoryaccording to claim 1, wherein said base ingredient for retaining thesuppository in the lower region of the rectum is one or more membersselected from the group consisting of a carboxyvinyl polymer, methylcellulose, and carboxymethylcellulose.
 4. A suppository according toclaim 1, wherein said suppository base further comprises a powderinsoluble in fatty acid triglyceride.
 5. A suppository according toclaim 1, wherein said suppository base further comprises anhydroussilicic acid.
 6. A suppository according to claim 1, wherein totalC₁₀₋₁₂ fatty acid glyceride in the suppository base is less than 1% ofthe total weight of the suppository base.
 7. The suppository of claim 1,wherein said one or more active ingredients are present in an amount offrom 0.1–20% of the total weight of the suppository.
 8. The suppositoryof claim 1, wherein said fatty acid triglyceride is present in an amountof from 65–85% of the total weight of the suppository base.
 9. Thesuppository of claim 8, wherein said one or more C₁₄₋₁₈ fatty acidglycerides is present in an amount of from 6.5–13% of the total weightof the suppository base.
 10. The suppository of claim 9, wherein saidbase ingredient for retaining the suppository in the lower region of therectum is present in an amount of from 1–10% of the total weight of thesuppository base.